The proposed EHS Center will enhance cooperative research at the University of Wisconsin-Madison that addresses molecular mechanisms by which environmental toxicants disrupt developmental processes. The Center involves 31 Investigators. Investigators are divided among three Research Cores (RCs): 1) effects of toxicants on development, 2) toxicity mediated by receptors, and 3) reactive intermediates. These research activities will be supported by five Facility and Services Cores: Microanatomy (embryo systems, microdissection, histology), Transgenic Animals (gene deletion and specific expression in mice and rats), Advanced Microscopy, Biomarkers (mass spectrometry of metabolites, adducts, and peptides; profiling and quantitation of toxicant induced changes in protein and RNA), and Molecular Biology (gene cloning and expression; sequencing). RCs will assist in creating focal research areas involving six to nine Investigators that will address toxicological problems that benefit from a multi-Investigator approach. Six focal groups have been identified: developmental target organ toxicity, endocrine disruption, early initiation of breast cancer, oxidant stress and developmental roles of Ah receptors, and liver development. Cooperative research will be enhanced by joint Research Core Workshops, focal group meetings, invited seminars, and an annual symposium on Developmental Toxicology and an Annual Retreat. FSCs will enhance the development and transfer of new technology while assisting with standard protocols. Recruitment of new members and generation of new projects will be promoted by startup funding and a Pilot Project program. Transfer of education materials and advice about toxicology to State agencies and regional schools, business, and media will be coordinated by the Center Outreach and Education Program (COEP), which will also facilitate interactions between Center Investigators and three toxicology-related public health projects. The COEP will work in conjunction with the existing Biotechnology Outreach Program and the Center for Biology Education. The Director of the EHS Center will report to the Dean of the Graduate School. Leadership by the Director will be carried out in conjunction with the Internal Advisory Committee (consisting of Core Leaders and Business Manager) assisted by campus Scientific Advisory and Administrative Committees, and an External Advisory Committee (experts in Center administration and developmental toxicology). Daily operation of the Center, planning (budgets, record- keeping, review), and the Annual Report will be coordinated by the Administrative Core supervised by the Business Manager and the Director. Center communication will be facilitated by a quarterly newsletter and a Center Website. The EHS Center will cooperate with other campus Centers (e.g. McArdle Laboratory for Cancer Research, Biotechnology Center) to optimize use of resources.